Comparative assessment of external apical root resorption between subjects treated with clear aligners and fixed orthodontic appliances: A systematic review and meta-analysis

This review aims to collate and analyze the existing evidence on the comparison of external apical root resorption (EARR) in subjects treated with clear aligners (CAs) and fixed appliances (FA). An electronic search was conducted in six databases for articles published in all languages until July 2023. Studies that evaluated EARR in subjects treated with CAs and FAs were included. The RoB 2 tool for RCTs and the ROBINS-I tool for non-randomized studies were used to analyze the risk of bias (ROB). A random effects meta-analysis was performed to assess EARR extent in maxillary and mandibular anterior teeth for subjects treated with CAs and FAs. Ten studies (eight retrospective, one RCT, and one CCT) were included in this review, out of which six studies reported a moderate ROB, one reported a serious ROB, and three reported a low ROB on qualitative analysis. The quantitative analysis of six studies revealed a significant intergroup difference (P<0.05) in the mean EARR for maxillary central (SMD=-0.62, P<0.00001) and lateral incisors (SMD=-0.47, P=0.01) with a moderate heterogeneity (I2=56%), as well as the mandibular central incisors (SMD=-0.27, P=0.04) with high heterogeneity (I2=79%). EARR was lower in subjects treated with CAs than FAs. A moderate quality of the available evidence suggests that EARR was less evident in subjects treated with CAs when compared with FAs.


Introduction
External apical root resorption (EARR) is a frequent consequence of orthodontic treatment. 1Cemental or surface resorption with remodeling, dentinal resorption with repair, and circumferential apical root resorption with root shortening have been documented as the three types of orthodontically induced inflammatory EARR. 2 Although orthodontic treatment is an iatrogenic cause of EARR, various other factors, including genetic vulnerability, mechanical causes, and individual biological variance, have been reported. 3,4ubjects undergoing protracted orthodontic treatment involving tooth extraction to gain space are prone to a higher incidence of EARR. 5 Since most of these changes are irreversible and may impact tooth longevity, clinicians must recognize them during orthodontic treatment. 6ARR can be diagnosed using intraoral periapical radiographs (IOPAs), orthopantomograms (OPGs), or cone-beam computed tomography (CBCT). 7lear aligners (CAs) are transparent removable appliances and are alternatives for fixed orthodontic appliances (FA) to treat malocclusions.They have become very popular recently, particularly among adult patients. 8ompared with fixed orthodontic appliances, CAs are more comfortable, aesthetically pleasing, hygienic, and less painful and need fewer and shorter consultations. 8As are very different from FAs in terms of attachment to the teeth, biomechanics, and treatment duration; hence, we can expect differences in EARR between them.
Previous systematic reviews have reported on the incidence of root resorption with CA therapy, and a comparison with FAs has been attempted. 9,10Both these reviews presented a few limitations and shortcomings; hence, we sought to update the relevant literature and address the limitations.In both reviews, studies assessing EARR individually in CAs and FAs and comparative studies were included, contributing to bias; most studies reported using either OPGs or IOPAs, and a few studies reported CBCTs for examining EARR.Recently, many studies have been published employing CBCTs for evaluating EARR; therefore, it is pertinent to update the existing reviews.The present review aimed to collect and analyze literature specifically on the comparative assessment of EARR following treatment with CA and FA.
The null hypothesis: There is no difference in EARR in subjects treated with CAs and FA

Protocol and registration
The PRISMA 2020 statement's reporting standards for systematic reviews and meta-analyses were followed in the reporting of this study.This systematic review was submitted to the International Prospective Register of Systematic Reviews -PROSPERO database and given a registration number -CRD42023448412.

Search strategy
An electronic search of the literature published in the below-mentioned databases was carried out to identify all papers related to the research question: Google Scholar, PubMed, Scopus, Cochrane, and Cochrane Embase.Open Grey and GreyNet International were searched for grey literature.Key words were modified for each database (Table 1).The search was conducted for articles published until July 2023 in all languages.Rayyan's duplicate removal tool was used. 11igibility criteria Randomized controlled trials, prospective studies, and retrospective studies were included.Review articles, letters to the editor, and case reports/series studies were excluded.Studies involving patients treated with both CAs and FAs in separate groups were included.Both before and after treatment, IOPA, OPG, or CBCT had to be available to measure EARR.In all the included studies, only subjects with dental root maturity were assessed.EARR had been reported in the included studies as a percentage or mm change in root length after treatment: • Population: Subjects undergoing orthodontic treatment • Intervention: Clear aligners • Control: Fixed appliances • Outcome: External apical root resorption

Screening and selection of studies
All studies that met the selection criteria were included in the review.The PRISMA flow chart shows the procedure for choosing the studies for the review (Figure 1).The selection of the studies, tabulation, and the RoB assessment were performed by both authors (SS and RKJ).Any differences were discussed with the third author (AB) and resolved.The characteristics table included the following general data from the included studies: First

Qualitative assessment of the included studies
The Cochrane RoB 2 tool was used for RCTs, while the ROBINS-I tool was utilized for qualitative evaluation of non-randomized trials.The biases included by the ROBINS-I tool are confounding, bias in participant selection, bias in the classification of interventions, bias due to deviations from intended interventions, bias introduced by missing data, bias in outcome measurement, bias in result reporting, and overall bias.When assessing the bias in the RCT, bias resulting from the randomization process, bias due to deviations from the intended interventions (effect of assignment to intervention), bias due to missing outcome data, bias in the measurement of the outcome, and bias in the selection of the reported result were all considered.Each signaling question was reported as "partially yes, " "yes, " "no, " "partially no, " or "not indicated." The ROB analysis of the retrospective studies is summarized in Figures 2 and 3.Both authors (SS and RKJ) worked independently and reviewed all the included studies for their qualitative assessment.Any conflict was resolved by mutual discussion.

Quantitative assessment of the included studies
Using the Cochrane Review Manager software (Revman Web), a meta-analysis of the mean and standard deviation of the primary outcome was carried out.A random effects model (DerSimonian-Laird random effects pooling approach) was used to compute the overall effects.A subgroup meta-analysis with a pooled mean difference was conducted.The EARR was quantified as a mean mm or %.Some of the articles included various measuring tools for EARR.A funnel plot was used to determine publication bias.

Statistical analysis
The outcome measure evaluated was EARR, measured as a reduction in root length in mm or percentage.Outcome data of root length reduction in mm was pooled from the included studies and analyzed using weighted mean difference with a 95% confidence interval.Heterogeneity was assessed using I-squared (I 2 ) tests.Sensitivity analysis was performed by deleting each study individually to detect the quality and consistency of the results.A randomeffects model of meta-analysis was used for quantitative analysis.Forest plot analysis was used to determine the influence of each subgroup on heterogeneity.A funnel plot analysis was performed to assess publication bias.Revman Web software was used for the analysis mentioned above.

Study Selection
Authors SS and RKJ individually performed the screening and selected the studies according to the selection criteria.Any disagreements were resolved by consultation with the third author AB.The electronic search identified 260 articles.After removing the duplicates (n = 97) using the Rayyan software, 163 studies were assessed for title and abstract screening, of which 142 articles were excluded.
Of the 21 studies, after excluding 11 studies for various reasons, 10 studies were included in the qualitative analysis, and out of them, six were subjected to quantitative analysis (as depicted in Figure 1).

Study characteristics
The detailed characteristics of the included studies are presented in Table 2, providing all details about the authors, study design, number of participants, treatment duration, type of malocclusion, and the outcomes assessed (root resorption in maxillary and mandibular anterior teeth).

Risk of bias analysis
The RCT by Toyokawa-Sperandio et al 12 had a low risk of bias (ROB) as assessed by the RoB-2 tool (Figure 2).19,21 low risk for two studies, 16,17 and serious 20 concerns for one study (Figure 3).

Result of the qualitative analysis
5][16][17][18][19][20][21] The remaining two studies reported similar EARR in patients treated with both CAs and FAs. 12,13The mean root resorption for the permanent maxillary incisors was in the range from 0.26 to 2.66 mm and 0.23 to 1.31 mm for permanent maxillary lateral incisors, and 0.20 to 0.73 mm for mandibular central incisors, which were clinically significant.

Author and Year of Study Results (P value) Inference
None J et al, 2021 16 The mean value of EARR in FA was 1.51 ± 1.34 mm, and in CA was 1.12 ± 1.34 mm (P < 0.001) CAs showed less EARR than FAs.
The patients treated with CAs had a lower prevalence and severity of EARR than FA.
Li et al, 2018 17 Compared to the FA group (6.97 ± 3.67%), the mean value of EARR in the CA group was much lower at (5.13 ± 2.81%) which was statistically significant (P < 0.05).Subjects treated with CAs had reduced EARR Chen et al, 2022 18 Root length and volume loss were less in CA (23.68 ± 4.82 mm 3 ) followed by FA (28.24 ± 6.44 mm 3 ) which was statistically significant (P < 0.05) CA-treated subjects showed less incidence of fenestration and root resorption Almagrami et al, 2023 19 EARR in the CA group was significantly less (0.31 ± 0.42) than those in the FA group (0.68 ± 0.97) (P < 0.000) CAs and FAs appear to cause a significant alveolar bone thickness reduction.Increased EARR in the maxillary incisor region with FAs was noted.
Wang et al, 2017 20 EARR occurred in 47.3% of teeth in the CA group and 68.8% in the FA group with a significant intergroup difference (P < 0.05).
CAs resulted in less root resorption than FAs.
Iglesias-Linares, 2017 13 The final associations between clinical and genetic factors and predisposition to EARR showed no statistically significant differences (P > 0.05) about EARR or the type of orthodontic appliance used (OR:   leading to less EARR when compared with FAs. 22With aligners, forces created are light and intermittent as they are removed during food consumption to maintain oral hygiene.With interrupted forces, less EARR was observed during orthodontic treatment according to the study by Sawicka et al, 23 and the risk of EARR increases by recurrent tooth movement brought on by jiggling forces.Non-extraction treatment strategy, a shorter course of treatment, and less root movement during orthodontic therapy may contribute to non-significant EARR with either CA or FA. 9,10FAs are better at torque control/ buccolingual inclination and root angulation than CAs.Hence, we can infer that since torque control, buccolingual movements, and root movements are less effective with CAs, the incidence of EARR is also less with CAs. 24lso, preplanning and staging various tooth movements is done in CAs; hence, the possibility of multiple tooth movements at a single point in time, subjecting the teeth to unpredictable forces, is very remote.CAs rely on patient compliance; hence, whenever patients are not using them, cementum repair takes place, which is not seen with FAs. 25 In one of the investigations, it was reported that refinements during CA treatment reduce the risk of EARR.Because CAs are worn intermittently and retainers are prescribed before refinements, repair following root resorption is achievable with CAs.This may also be one of the causes of the decreased prevalence of EARR in CAs. 14 Most of the retrospective studies included in this review had a moderate to low ROB, while the RCT had a low ROB.Deviation from intended interventions contributed to bias in some of the included retrospective studies.Previous published systematic reviews on the comparison of root resorption between CA and FA reported some limitations; hence, this review was undertaken.Previously published reviews have not included studies with both CA and FA groups.A review by Fang et al. 9,10 included three studies employing CBCT as a tool for EARR assessment, whereas six studies in this review reported using CBCT.CBCT is more reliable for measuring EARR than IOPAs or OPGs.In the present study, CBCT data from five studies were subjected to a subgroup meta-analysis of individual teeth.Two studies included in this review had EARR data of extraction cases with higher crowding and treatment duration, reducing bias. 17,19The systematic review by Gandhi et al 9 included studies that investigated EARR in patients who underwent FA therapy without extractions using FAs or CAs by either CBCT or 2D radiographic examination, unlike the present review. 10Except for two studies in their review, patients treated with either CAs or FAs were evaluated separately for EARR.In the present ystematic review, all the included studies had subjects treated with CAs and FAs, hence avoiding pooling data from different studies in different setups and on different populations. In the present review, the quantitative assessment of EARR between CAs and FAs showed a significant mean difference for maxillary central incisor and lateral incisor with less incidence of EARR in CAs, which are not consistent with the findings of a review by Gandhi et al. 9 Although there was no significant difference between FA and CA for EARR of teeth #22, #12, and #23 in their review (P > 0.05), the subjects treated with FA had significantly more root resorption than the subjects treated with CA for upper right lateral incisor teeth.In the review by Fang et al, 10 individual incisor teeth showed significantly less EARR with CAs compared to FA for all maxillary incisors, which is consistent with the present study.As treatment duration is a factor influencing EARR, it was noted in the present review that in all included studies, the treatment duration was roughly similar for subjects treated with both CAs and FAs. 9,10The treatment duration or the assessment period for CAs in the included studies was as short as six months 11 and as long as 30.94 ± 4.32 months, 19 and for FA, it was as short as six months 11 and as long as 29.67 ± 7.7 months.Therefore, intergroup differences in treatment duration will not influence the severity of EARR.Root volume was measured in only one of the included studies, and it was shown that participants who received CAs showed much less root volume reduction than those who received FAs.Additionally, the CA group experienced a higher increase in labial bone thickness at the apical level.

Limitations
Only one RCT was included, and most included studies were retrospective with a moderate ROB.The results of this research must be employed carefully because separate investigations have used various diagnostic modalities for the same examined measurements, which contributes to heterogeneity.The included articles involved a combination of different aligners and both conventional edgewise and pre-adjusted edgewise and self-ligating appliances, which might lead to differences in root resorption.

Conclusion
The following conclusions can be drawn from the present review considering its limitations: 1. Moderate-quality evidence suggests that the extent and severity of EARR were lower in subjects treated with CAs than in subjects treated with FAs. 2. On quantitative assessment, maxillary central and lateral incisors and mandibular central incisors exhibited significantly less EARR in subjects treated with CAs.

Figure 1 .
Figure 1.PRISMA flow diagram for study selection

Figure 4 .
Figure 4. Forest plot of EARR in the maxillary anterior teeth

Figure 5 .
Figure 5. Forest plot of EARR in the mandibular anterior teeth

Figure 6 .
Figure 6.Funnel plot for publication bias of studies reporting on EARR of maxillary anterior teeth

Figure 7 .
Figure 7. Funnel plot for publication bias in studies that report EARR of mandibular incisors
DiscussionEARR is a well-documented consequence of orthodontic treatment involving both fixed and removable appliances.This systematic review was carried out to gather, compile, and analyze data on the extent and severity of EARR in patients treated with CAs and compare it with patients treated with FAs from human clinical trials published as retrospective studies and randomized and nonrandomized trials.This review involved only studies with CAs as an intervention and FAs as a comparison or control group.A total of ten studies reported on EARR of various teeth individually with IOPA, CBCT, and OPG in millimeters, percentages, or volume.Both qualitative and quantitative analyses revealed a lower overall incidence of EARR in subjects treated with CAs than in those treated with FAs.On analyzing the individual teeth for EARR, it was noted that maxillary central and lateral incisors had less EARR in subjects treated with CAs than in subjects treated with FAs.Concerning mandibular teeth, central incisors had less incidence of EARR in subjects treated with CAs than in subjects treated with FAs.Different mechanical aspects between CAs and FAs contribute to changes in EARR.Aligners, if well tolerated by patients, result in predictable tooth movement, EARR: External apical root resorption; CA: Clear aligners; FA: Fixed Orthodontic Appliances; OR: Odds Ratio, CI: Confidence interval.